We propose to complete an age-29 assessment of female twin participants in the Minnesota Twin Family Study (MTFS). The resulting data will allow us to investigate the developmental processes that link adolescent substance abuse with diverse adult outcomes and explore the mechanisms of substance abuse desistence in early adulthood. The female portion of the MTFS is based on 717 pairs of female twins and their parents drawn from two population-based cohorts. The older twin cohort, originally seen at age 17 and followed up at ages 20 and 24, has completed the age-29 assessment. The younger cohort, originally recruited at age 11, before the initiation of significant substance use, has completed follow-ups at ages 14, 17, 20, and 24, and will be followed through age 29. The age-29 assessment is focused on outcomes potentially associated with adolescent substance use and risk and protective factors that might influence substance abuse desistence. Data from both cohorts will be combined to examine the developmental trajectories leading to differences in mental health, social, and neurocognitive outcomes at age 29. In addition, we will identify factors associated with desistance of substance abuse in early adulthood and determine whether desistence ameliorates the negative influence of adolescent-onset abuse on adult outcomes. Importantly, a comparison of findings from this study with those from a funded parallel study in male twins (DA05417) will allow us to explore gender differences in the effects of adolescent substance abuse on adult functioning and in desistence processes in early adulthood. Participants have completed a comprehensive longitudinal assessment, including information from multiple informants (parents, teachers, co-twins), that begins in adolescence or earlier for both cohorts. Our developmentally rich data set measures the initiation and progression of tobacco, alcohol, and illicit drug use; externalizing and internalizing psychopathology; biological indices of risk (e.g., brain event-related potentials, resting EEG, genetic polymorphisms); personality traits; and a wide array of experiential risks (e.g., life-event stress, family and peer relationships, social support, early exposure to substances). We will take advantage of our twin design to examine the contribution of gene-environment interplay in the development of adult adjustment, including making use of monozygotic co-twin controls to determine whether environmental differences in risk exposure (including differences in exposure to abused substances) over the course of development are associated with differences in outcome. The completion of this project will provide for a rigorous and comprehensive evaluation of the long-term effects of adolescent-onset substance abuse on functioning in early adulthood.